Dataset Information

Iron infusion in iron-deficient patients undergoing surgery for colorectal cancer who are anaemic versus not anaemic in order to improve physical fitness as determined by exercise testing and a quality of life questionnaire.

ABSTRACT: Intervention will occur independent of date of surgery. The follow-up date will occur before date of surgery. Control treatment will occur independent of date of surgery. The follow-up date will occur before date of surgery. This means that FCM will be administered at least 2 weeks before any further intervention, such as neoadjuvant chemotherapy or surgery. This will not cause any delay in normal treatment. After baseline CPX is performed (Day 0), participants will receive 1000mg of Ferric Carboxymaltose (FCM) in a maximum of 250mls of 0.9% saline solution; Ferinject, Vifor Pharma, Glattbrugg, Switzerland) over a 15 minute period. All patients will be monitored for 30 minutes following completion of the infusion. No further blood tests will be required on the day of the infusion. Adherence to FCM will be monitored as the patient will be monitored on the ward. Primary outcome(s): To assess if the preoperative functional status (as measured by CPX) of anaemic and/or iron deficient colorectal cancer patients will be improved following an intravenous infusion of FCM. The primary endpoint is the change in VO2peak measured by the CPX, from baseline CPX (Day 0) to CPX test #2 (Day 14) following a transfusion of FCM.[The primary endpoint is the change in VO2peak measured by the CPX, from baseline CPX (Day 0) to CPX test #2 (Day 14) following a transfusion of FCM.] Study Design: Purpose: Treatment; Allocation: Randomised controlled trial; Masking: Blinded (masking used);Assignment: Parallel;Type of endpoint: Efficacy

DISEASE(S): Blood-anaemia,Anaemia,Colorectal Cancer,Cancer-bowel-back Passage (rectum) Or Large Bowel (colon),Anaesthesiology-other Anaesthesiology,Iron Deficiency

PROVIDER: 2464262 | ecrin-mdr-crc |

REPOSITORIES: ECRIN MDR

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Project description:Endurance exercise improves cardiac performance and affords protection against cardiovascular diseases but the signalling events that mediate these benefits are largely unexplored. Phosphorylation is an widely studied post-translational modification involved in intracellular signalling, and to discover novel phosphorylation events associated with exercise we have profiled the cardiac phosphoproteome response to a standardised exercise test to peak oxygen uptake (VO2peak). Male Wistar rats (346 ± 18 g) were assigned to 3 independent groups (n= 6, in each) that were familiarised with running on a motorised treadmill within a metabolic chamber. Animals performed a graded exercise test and were killed either immediately (0 h) after or 3 h after terminating the test at a standardised physiological end point (i.e. peak oxygen uptake; VO2peak). Control rats were killed at a similar time of day to the exercised animals, to minimise possible circadian effects. Cardiac proteins were digested with trypsin and phosphopeptides were enriched by selective binding to titanium dioxide (TiO2). Phosphopeptides were analysed by liquid chromatography and high-resolution tandem mass spectrometry, and phosphopeptides were quantified by MS1 intensities and identified against the UniProt knowledgebase using MaxQuant (v1.3.0.5). The VO2peak of rats in the 0 h and 3 h groups was 66 ± 5 ml•kg-1•min-1 and 69.8 ± 5 ml•kg-1•min-1, respectively. Proteome profiling detected 1169 phosphopeptides and one-way ANOVA found 141 significant (P<0.05 with a false discovery rate of 10 %) differences. Almost all (97 %) of the phosphosites that were responsive to exercise are annotated in the PhosphoSitePlus database but, importantly, the majority of these have not previously been associated with the cardiac response to exercise. More than two-thirds of the exercise-responsive phosphosites were different from those identified in previous phosphoproteome profiling of the cardiac response to β1-adrenergic receptor stimulation. Moreover, we report entirely new phosphorylation sites on 4 cardiac proteins, including S81 of muscle LIM protein, and identified 7 exercise-responsive kinases, including myofibrillar protein kinases such as obscurin, titin and the striated-muscle-specific serine/threonine kinase (SPEG) that may be worthwhile targets for future investigation.

Dataset Information

Iron infusion in iron-deficient patients undergoing surgery for colorectal cancer who are anaemic versus not anaemic in order to improve physical fitness as determined by exercise testing and a quality of life questionnaire.

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